EBX-001 for Cystic Fibrosis Infections
A Critical Unmet Need in Cystic Fibrosis (CF):
Chronic, Recurrent Lung Infections Associated with Early Mortality:
- >80% of CF deaths attributable to progressive lung disease
- Most CF patients develop chronic Pseudomonas infections at an early age
- Inhaled tobramycin is a cornerstone of CF therapy
- Current antibiotic treatment fails to eradicate due to bacterial persisters
EBX-001 is a combination of tobramycin (TOB) with fumarate (as an antibacterial potentiator) for the eradication of P. aeruginosa (Pae) persisters. EBX-001 significantly enhances killing of Pae persisters through a novel proton-motive-force (PMF) enhancing mechanism. EBX-001 data show up to 6 orders-of-magnitude enhanced killing of Pae persisters over a range of CF isolates, including mucoid and non-mucoid strains, compared to TOBI alone, as well as complete eradication of Pae biofilms. EBX-001 is initially being developed for treatment of Pae infections in CF patients, although market expansion to non-CF bronchiectasis (nCFBE) and COPD is envisioned.
Dose-dependent fumarate potentiation on TOB sensitivity in Pae non-mucoid & mucoid CF isolates
Eradication of Pseudomonas mucoid and non-mucoid CF isolate colony biofilms
Koeva M, Gutu AD, Hebert W, Wager JD, Yonker LM, O’Toole GA, Ausubel FM, Moskowitz SM, Joseph-McCarthy D. 2017. An Antipersister Strategy for Treatment of Chronic Pseudomonas aeruginosa Infections. Antimicrob Agents Chemother 61:e00987-17.